Current approaches to prediabetes

Leszek Czupryniak, MD, PhD, is a professor of medicine and head of the Department of Diabetology and Internal Medicine at the Medical University of Warsaw, Poland. His areas of interest are type 1 diabetes, type 2 diabetes, diabetes accompanying other diseases, and chronic complications of diabetes, with special interest in oral antidiabetic agents and insulins.

What are the current pharmacologic treatment options to delay the onset of type 2 diabetes in patients with prediabetes?

Leszek Czupryniak, MD, PhD: The question seems to be easy, and we have the answer. We’ve been having the answer for the last 2 or 3 decades. The number 1 pharmacologic option to prevent diabetes if one has prediabetes is metformin. And that’s a no-brainer. The dose of 850 mg bid has been well studied and is approved to be used in prediabetes worldwide, practically.

But we do have newer agents for diabetes, such as glucagon-like peptide 1 (GLP-1) receptor agonists or analogues and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, which have been shown to be very effective in delaying the progression of the processes that lead from prediabetes to diabetes. However, they have not been properly studied in this indication, so we see the effect of these drugs either in obesity trials for GLP-1 analogues or in the trials with patients with heart failure or chronic kidney disease—they were given an SGLT-2 inhibitor (the drug was studied in this population). In these studies, half of the population did not have diabetes, they often had prediabetes. And it was very nicely shown that these drugs are also able to delay diabetes. So, it really depends on what we want. If we follow strictly the registration labels, we should stick to metformin only. But that is probably not the best option for the patients. We can use either virtually any SGLT-2 inhibitor or GLP-1 receptor agonist, with the ones given once weekly, like semaglutide, dulaglutide, or tirzepatide, which is a dual incretin receptor agonist. These drugs are also effective in preventing type 2 diabetes, but it’s not on the label that patients would be informed that these drugs are prescribed in this indication. And, of course, there will be no reimbursement for these drugs in these indications because there is nothing in the product characteristics.

We have to keep open minds, as this area of preventing diabetes with pharmacology is evolving fast, much faster than any legal regulations in this regard. But I’m strongly convinced that limiting the options just to metformin is obsolete, old fashioned, and as much as metformin, of course, can and should be used in this population with prediabetes, we can offer these patients much, much more with either SGLT-2 inhibitors or GLP-1 analogues.